Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR1667)
Drug Name
Valproic acid
Synonyms
Valproate; Valproinsaeure; Vupral; Acide valproique; Acido valproico; Acidum valproicum; Avugane; Baceca; Convulex; Depakene; Depakin; Depakine; Deproic; Di-n-propylacetic acid; Di-n-propylessigsaure; Dipropylacetate; Dipropylacetic acid; Ergenyl; Kyselina 2-propylvalerova; Mylproin; Myproic Acid; Pentanoic acid, 2-propyl-; Propylvaleric acid; Stavzor; VALPROIC ACID; n-Dipropylacetic acid; 2-Propylpentanoic acid; 2-Propylvaleric acid; 2-n-Propyl-n-valeric acid; 4-Heptanecarboxylic acid; 99-66-1; Abbott 44090; Acetic acid, dipropyl-; n-DPA
Indication Epilepsy [ICD11: 8A60] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 144.21 Topological Polar Surface Area 37.3
Heavy Atom Count 10 Rotatable Bond Count 5
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 2
Cross-matching ID
PubChem CID
3121
PubChem SID
9394 ; 399407 ; 621684 ; 3138784 ; 4918409 ; 7847465 ; 7980632 ; 8151988 ; 10539166 ; 11335448 ; 11360687 ; 11363415 ; 11364691 ; 11365977 ; 11367253 ; 11368539 ; 11369815 ; 11372725 ; 11372856 ; 11374010 ; 11375415 ; 11376701 ; 11377978 ; 11461659 ; 11484648 ; 11488762 ; 11491548 ; 11492191 ; 11494335 ; 12015354 ; 14710660 ; 15321539 ; 17389523 ; 24898751 ; 26697333 ; 26752920 ; 26752921 ; 29222263 ; 46260925 ; 46505925 ; 48416692 ; 48424277 ; 48425730 ; 49635685 ; 49640649 ; 49856166 ; 50062089 ; 50105536 ; 53788878 ; 56310655
ChEBI ID
CHEBI:39867
CAS Number
76584-70-8
TTD Drug ID
D0Y3KG
Formula
C8H16O2
Canonical SMILES
CCCC(CCC)C(=O)O
InChI
1S/C8H16O2/c1-3-5-7(6-4-2)8(9)10/h7H,3-6H2,1-2H3,(H,9,10)
InChIKey
NIJJYAXOARWZEE-UHFFFAOYSA-N
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
(3E)-2-Propylpent-3-enoic acid DM002450
6439747
Unclear 1 [5]
(3Z)-2-Propylpent-3-enoic acid DM002449
24892812
Oxidation - Dehydrogenation 1 [5]
2-ene-VPA DM002447
6437068
Oxidation - Dehydrogenation 1 [5]
3-OH-VPA DM002445
134459
Unclear 1 [5]
4-ene-VPA DM002441
104896
Oxidation - 3-Hydroxylation 1 [5]
4-OH-VPA DM002438
134467
Oxidation - 4-Hydroxylation 1 [5]
5-OH-VPA DM002443
135244
Oxidation - 5-Hydroxylation 1 [5]
Valproic acid beta-O-glucuronide metabolite DM002448
88111
Oxidation - Dehydrogenation 1 [5]
Valproic acid CoA DM002451
131769983
Unclear 1 [9]
2,4-Diene-VPA DM002442
6441809
Unclear 2 [5]
2-N-Propyl-4-oxopentanoic acid DM002439
3731686
Oxidation - Dehydrogenation 2 [5] , [9]
2-Propylglutaric acid DM002444
134970
Oxidation - Dehydrogenation 2 [5]
3-OH-VPA DM002445
134459
Unclear 2 [5]
3-Oxovalproic acid DM002446
173719
Unclear 2 [5]
2-Propylsuccinic acid DM002440
3031829
Oxidation - 5-Hydroxylation 3 [5]
⏷ Show the Full List of 15  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR002492 Valproic acid 4-hydroxyvalproic acid Oxidation - 4-Hydroxylation CYP2B6 ... [5]
MR002493 Valproic acid 4-ene-Valproic acid Oxidation - 3-Hydroxylation CYP2B6 ... [5]
MR002494 Valproic acid 5-hydroxyvalproic acid Oxidation - 5-Hydroxylation CYP2B6 ... [5]
MR002495 Valproic acid 3-hydroxyvalproic acid Unclear CYP3A5 ... [5]
MR002496 Valproic acid 2-ene-Valproic acid Oxidation - Dehydrogenation Unclear [5]
MR002497 Valproic acid Valproic acid beta-O-glucuronide metabolite Oxidation - Dehydrogenation UGT1A10 ... [5]
MR002498 Valproic acid (3Z)-2-Propylpent-3-enoic acid Oxidation - Dehydrogenation Unclear [5]
MR002499 Valproic acid (3E)-2-Propylpent-3-enoic acid Unclear Unclear [5]
MR002500 Valproic acid Valproic acid CoA Unclear Unclear [9]
MR002491 2-ene-Valproic acid 3-hydroxyvalproic acid Unclear Unclear [5]
MR002490 3-hydroxyvalproic acid 3-Oxovalproic acid Unclear Unclear [5]
MR002488 4-ene-Valproic acid 2,4-Diene-VPA Unclear Unclear [5]
MR002486 4-hydroxyvalproic acid 2-N-Propyl-4-oxopentanoic acid Oxidation - Dehydrogenation Unclear [5], [9]
MR002489 5-hydroxyvalproic acid 2-Propylglutaric acid Oxidation - Dehydrogenation Unclear [5]
MR002487 2-N-Propyl-4-oxopentanoic acid 2-Propylsuccinic acid Oxidation - 5-Hydroxylation CYP2B6 ... [5]
⏷ Show the Full List of 15 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 2A6 (CYP2A6) DME0005 Homo sapiens
CP2A6_HUMAN
1.14.14.1
[2]
Cytochrome P450 2B6 (CYP2B6) DME0020 Homo sapiens
CP2B6_HUMAN
1.14.14.1
[3]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[4]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[5]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[4]
Prostaglandin G/H synthase 1 (COX-1) DME0091 Homo sapiens
PGH1_HUMAN
1.14.99.1
[5]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[6]
UDP-glucuronosyltransferase 1A10 (UGT1A10) DME0075 Homo sapiens
UD110_HUMAN
2.4.1.17
[7]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DME0041 Homo sapiens
UD13_HUMAN
2.4.1.17
[6]
UDP-glucuronosyltransferase 1A6 (UGT1A6) DME0072 Homo sapiens
UD16_HUMAN
2.4.1.17
[7]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DME0042 Homo sapiens
UD19_HUMAN
2.4.1.17
[5]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DME0040 Homo sapiens
UD2B7_HUMAN
2.4.1.17
[8]
⏷ Show the Full List of 12  DME(s)
References
1 Valproic Acid was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Psychotropic drug interactions with valproate. Clin Neuropharmacol. 2005 Mar-Apr;28(2):96-101.
3 Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425.
4 A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
5 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
6 Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
7 UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: II. Functional impact of the three most common nonsynonymous UGT1A6 polymorphisms (S7A, T181A, and R184S). J Pharmacol Exp Ther. 2005 Jun;313(3):1340-6.
8 Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects. Clin Pharmacol Ther. 2008 Apr;83(4):595-600.
9 PharmGKB: the Pharmacogenomics Knowledge Base Methods Mol Biol. 2013;1015:311-20. doi: 10.1007/978-1-62703-435-7_20.

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